tbuckley/cabot-search huggingface dataset:
Risk factors for postoperative surgical site infections after anterior cruciate ligament reconstruction: a systematic review and meta-analysis
Authors: Di Zhao, Gui-Hong Liang, Jian-Ke Pan, Ling-Feng Zeng, Ming-Hui Luo, He-Tao Huang, Yan-Hong Han, Fang-Zheng Lin, Nan-Jun Xu, Wei-Yi Yang, Jun Liu
Journal: British Journal of Sports Medicine (2022)

Objectives The primary aim was to evaluate risk factors for surgical site infections after anterior cruciate ligament reconstruction (ACLR). The secondary aim was to investigate the surgical site infection incidence rate and the mean time to postoperative surgical site infection symptoms. Design Systematic review and meta-analysis. Data sources PubMed, Embase and Web of Science were searched from database inception to September 2021 and updated in April 2022. Eligibility criteria Quantitative, original studies reporting potential risk factors for surgical site infections after ACLR were included. Results Twenty-three studies with 3871 infection events from 469 441 ACLRs met the inclusion criteria. Male sex (OR 1.78, p&lt; 0.00001), obesity (OR 1.82, p=0.0005), tobacco use (OR 1.37, p=0.01), diabetes mellitus (OR 3.40, p=0.002), steroid use history (OR 4.80, p&lt;0.00001), previous knee surgery history (OR 3.63, p=0.02), professional athlete (OR 4.56, p=0.02), revision surgery (OR 2.05, p=0.04), hamstring autografts (OR 2.83, p&lt;0.00001), concomitant lateral extra-articular tenodesis (OR 3.92, p=0.0001) and a long operating time (weighted mean difference 8.12, p=0.005) were identified as factors that increased the risk of surgical site infections (superficial and deep) after ACLR. Age, outpatient or inpatient surgery, bone-patellar tendon-bone autografts or allografts and a concomitant meniscus suture did not increase the risk of surgical site infections. The incidence of surgical site infections after ACLR was approximately 1% (95% CI 0.7% to 1.2%). The mean time from surgery to the onset of surgical site infection symptoms was approximately 17.1 days (95% CI 13.2 to 21.0 days). Conclusion Male sex, obesity, tobacco use, diabetes mellitus, steroid use history, previous knee surgery history, professional athletes, revision surgery, hamstring autografts, concomitant lateral extra-articular tenodesis and a long operation time may increase the risk of surgical site infections after ACLR. Although the risk of surgical site infections after ACLR is low, raising awareness and implementing effective preventions for risk factors are priorities for clinicians to reduce the incidence of surgical site infections due to its seriousness.
Plasma thymic stromal lymphopoietin (TSLP) in adults with non-severe asthma: the EGEA study
Authors: Bakari Ibrahim, Djamal Achour, Farid Zerimech, Patricia de Nadai, Valerie Siroux, Anne Tsicopoulos, Régis Matran, Vanessa Granger, Rachel Nadif
Journal: Thorax (2022)

Thymic stromal lymphopoietin (TSLP), a cytokine involved in severe asthma treatment, was never studied in non-severe asthma. Among 969 adults from a large epidemiological study, cross-sectional analyses showed that plasma TSLP levels were associated with increased age and BMI, male sex, smoking and high TSLP levels (one IQR increase) with current asthma and poor lung function. High TSLP levels were also associated with persistence of asthma attacks (aOR=2.14 (95% CI 1.23 to 3.72)) and dyspnoea (aOR=2.71 (95% CI 1.39 to 5.28)) 10 years later. Our results suggest that TSLP could be a cytokine of interest in non-severe asthma, and its determinants of circulating levels could be considered in asthma management.
Vascular Inflammation During and After Community-Acquired Pneumonia as Measured by 18F-FDG-PET/CT Imaging
Authors: Kevin E. Boczar, Girish Dwivedi, Anahita Tavoosi, Julio A. Chirinos, Robert A. deKemp, Rob S.B. Beanlands, Vicente Corrales-Medina
Journal: JACC. Cardiovascular imaging (2022)
PFD-SENTINEL: Development of a screening tool for pelvic floor dysfunction in female athletes through an international Delphi consensus
Authors: Silvia Giagio, Stefano Salvioli, Tiziano Innocenti, Giulia Gava, Marco Vecchiato, Paolo Pillastrini, Andrea Turolla
Journal: British Journal of Sports Medicine (2022)

To develop a screening tool for pelvic floor dysfunction (PFD) in female athletes for use by sports medicine clinicians (eg, musculoskeletal/sports physiotherapists, sports and exercise medicine physicians), which guides referral to a PFD specialist (eg, pelvic floor/women’s health physiotherapist, gynaecologist, urogynaecologist, urologist). Between February and April 2022, an international two-round modified Delphi study was conducted to assess expert opinion on which symptoms, risk factors and clinical and sports-related characteristics (items) should be included in a screening tool. We defined consensus a priori as &gt;67% response agreement to pass each round. 41 and 34 experts participated in rounds 1 and 2, respectively. Overall, seven general statements were endorsed as relevant by most participants highlighting the importance of screening for PFD in female athletes. Through consensus, the panel developed the Pelvic Floor Dysfunction-ScrEeNing Tool IN fEmale athLetes (PFD-SENTINEL) and agreed to a cluster of PFD symptoms (n=5) and items (risk factors, clinical and sports-related characteristics; n=28) that should prompt specialist care. A clinical algorithm was also created: a direct referral is recommended when at least one symptom or 14 items are reported. If these thresholds are not reached, continuous monitoring of the athlete’s health is indicated. Despite increasing awareness and clinical relevance, barriers to identify PFD in female athletes are still present. The PFD-SENTINEL is a new resource for sports medicine clinicians who regularly assess female athletes and represents the first step towards early PFD identification and management. Further studies to validate the tool are needed.
Associations of Mid- and Late-Life Severe Hypoglycemic Episodes With Incident Dementia Among Patients With Type 2 Diabetes: A Population-Based Cohort Study
Authors: Wajd Alkabbani, Colleen J. Maxwell, Ruth Ann Marrie, Suzanne L. Tyas, Iliana C. Lega, John-Michael Gamble
Journal: Diabetes Care (2022)

OBJECTIVE Severe hypoglycemia is associated with an increased risk of dementia. We examined if the association is consistently present in mid- and late-life hypoglycemia. RESEARCH DESIGN AND METHODS Using health care data from Population Data BC, we created a base cohort of patients age ≥40 years with incident type 2 diabetes. Exposure was the first occurrence of severe hypoglycemia (hospitalization or physician visit). We assessed exposure versus no exposure in mid- (age 45–64 years) and late-life (age 65–84 years) cohorts. Index date was the later of the 45th birthday (midlife cohort), 65th birthday (late-life cohort), or diabetes diagnosis. Those with hypoglycemia or dementia before the index date were excluded. Patients were followed from index date until dementia diagnosis, death, emigration, or 31 December 2018. Exposure was modeled as time dependent. We adjusted for confounding using propensity score weighting. Dementia risk was estimated using cause-specific hazards models with death as a competing risk. RESULTS Of 221,683 patients in the midlife cohort, 1,793 experienced their first severe hypoglycemic event. Over a median of 9.14 years, 3,117 dementia outcomes occurred (32 among exposed). Of 223,940 patients in the late-life cohort, 2,466 experienced their first severe hypoglycemic event. Over a median of 6.7 years, 15,997 dementia outcomes occurred (158 among exposed). The rate of dementia was higher for those with (vs. without) hypoglycemia in both the mid- (hazard ratio 2.85; 95% CI 1.72–4.72) and late-life (2.38; 1.83–3.11) cohorts. CONCLUSIONS Both mid- and late-life hypoglycemia were associated with approximately double the risk of dementia, indicating the need for prevention throughout the life course of those with diabetes.
A humanized mouse model to study NK cell biology during HIV infection
Authors: Jocelyn T. Kim, Jerome A. Zack
Journal: Journal of Clinical Investigation (2022)

NK cells are an important subset of innate immune effectors with antiviral activity. However, NK cell development and immune responses in different tissues during acute and chronic HIV infection in vivo have been difficult to study due to the impaired development and function of NK cells in conventional humanized mouse models. In this issue of the JCI, Sangur et al. report on a transgenic MISTRG-6-15 mouse model with human IL-6 and IL-15 knocked into the previously constructed MISTRG mice. The predecessor model was deficient in Rag2 and γ chain (γc) with knock-in expression of human M-CSF, IL-3, GM-CSF, and TPO, and transgenic expression of human SIRPα. The researchers studied tissue-specific NK cell immune responses during HIV infection and clearly show that the endogenous human NK cells in the humanized mouse model suppressed HIV-1 replication in vivo. These findings provide insight into harnessing the innate immune response for clinical antiviral therapies.
Delivery of costimulatory blockade to lymph nodes promotes transplant acceptance in mice
Authors: Jing Zhao, Sungwook Jung, Xiaofei Li, Lushen Li, Vivek Kasinath, Hengcheng Zhang, Said N. Movahedi, Ahmad Mardini, Gianmarco Sabiu, Yoonha Hwang, Vikas Saxena, Yang Song, Bing Ma, Sophie E. Acton, Pilhan Kim, Joren C. Madsen, Peter T. Sage, Stefan G. Tullius, George C. Tsokos, Jonathan S. Bromberg, Reza Abdi
Journal: Journal of Clinical Investigation (2022)

The lymph node (LN) is the primary site of alloimmunity activation and regulation during transplantation. Here, we investigated how fibroblastic reticular cells (FRCs) facilitate the tolerance induced by anti-CD40L in a murine model of heart transplantation. We found that both the absence of LNs and FRC depletion abrogated the effect of anti-CD40L in prolonging murine heart allograft survival. Depletion of FRCs impaired homing of T cells across the high endothelial venules (HEVs) and promoted formation of alloreactive T cells in the LNs in heart-transplanted mice treated with anti-CD40L. Single-cell RNA sequencing of the LNs showed that anti-CD40L promotes a Madcam1+ FRC subset. FRCs also promoted the formation of regulatory T cells (Tregs) in vitro. Nanoparticles (NPs) containing anti-CD40L were selectively delivered to the LNs by coating them with MECA-79, which binds to peripheral node addressin (PNAd) glycoproteins expressed exclusively by HEVs. Treatment with these MECA-79-anti-CD40L-NPs markedly delayed the onset of heart allograft rejection and increased the presence of Tregs. Finally, combined MECA-79-anti-CD40L-NPs and rapamycin treatment resulted in markedly longer allograft survival than soluble anti-CD40L and rapamycin. These data demonstrate that FRCs are critical to facilitating costimulatory blockade. LN-targeted nanodelivery of anti-CD40L could effectively promote heart allograft acceptance.
The rise of viperin: the emerging role of viperin in cancer progression
Authors: Alyssa G. Weinstein, Inês Godet, Daniele M. Gilkes
Journal: Journal of Clinical Investigation (2022)

Viperin, an IFN-regulated gene product, is known to inhibit fatty acid β-oxidation in the mitochondria, which enhances glycolysis and lipogenesis during viral infections. Yet, its role in altering the phenotype of cancer cells has not been established. In this issue of the JCI, Choi, Kim, and co-authors report on a role of viperin in regulating metabolic alterations in cancer cells. The authors showed a correlation between clinical outcomes and viperin expression levels in multiple cancer tissues and proposed that viperin expression was upregulated in the tumor microenvironment via the JAK/STAT and PI3K/AKT/mTOR/HIF-1α pathways. Functionally, viperin increased lipogenesis and glycolysis in cancer cells by inhibiting fatty acid β-oxidation. Viperin expression also enhanced cancer stem cell properties, ultimately promoting tumor initiation in murine models. This study proposes a protumorigenic role for viperin and identifies HIF-1α as a transcription factor that increases viperin expression under serum starvation and hypoxia.
Fibroblastic reticular cells orchestrate long-term graft survival following recipient treatment with CD40 ligand–targeted costimulatory blockade
Authors: Robert L. Fairchild
Journal: Journal of Clinical Investigation (2022)

Fibroblastic reticular cells (FRCs) maintain the architecture of secondary lymphoid organs, which optimize interactions between antigen-presenting dendritic cells and reactive naive T cells. In this issue of the JCI, Zhao, Jung, and colleagues investigated CD4+FoxP3+ regulatory T cell development and long-term heart allograft survival in recipients treated with peritransplant costimulatory blockade to inhibit CD40/CD40 ligand (CD40L) signaling. Treatment with an anti-CD40L monoclonal antibody (mAb) increased the lymph node (LN) population of Madcam1+ FRCs and altered their transcription profile to express immunoregulatory mediators. Administration of nanoparticles, containing the anti-CD40L mAb and a targeting antibody against high endothelial venules, delivered the treatment into LNs of allograft recipients. Direct LN delivery of the costimulatory blockade allowed decreased dosing and increased the efficacy in extending graft survival. The results provide insights into mechanisms by which FRCs can promote donor-reactive tolerance, and establish a strategy for administering costimulation-blocking reagents that circumvent systemic effects and improve allograft outcomes.
TIAM1-mediated synaptic plasticity underlies comorbid depression–like and ketamine antidepressant–like actions in chronic pain
Authors: Qin Ru, Yungang Lu, Ali Bin Saifullah, Francisco A. Blanco, Changqun Yao, Juan P. Cata, De-Pei Li, Kimberley F. Tolias, Lingyong Li
Journal: Journal of Clinical Investigation (2022)

Chronic pain often leads to depression, increasing patient suffering and worsening prognosis. While hyperactivity of the anterior cingulate cortex (ACC) appears to be critically involved, the molecular mechanisms underlying comorbid depressive symptoms in chronic pain remain elusive. T cell lymphoma invasion and metastasis 1 (Tiam1) is a Rac1 guanine nucleotide exchange factor (GEF) that promotes dendrite, spine, and synapse development during brain development. Here, we show that Tiam1 orchestrates synaptic structural and functional plasticity in ACC neurons via actin cytoskeleton reorganization and synaptic N-methyl-d-aspartate receptor (NMDAR) stabilization. This Tiam1-coordinated synaptic plasticity underpins ACC hyperactivity and drives chronic pain–induced depressive-like behaviors. Notably, administration of low-dose ketamine, an NMDAR antagonist emerging as a promising treatment for chronic pain and depression, induces sustained antidepressant-like effects in mouse models of chronic pain by blocking Tiam1-mediated maladaptive synaptic plasticity in ACC neurons. Our results reveal Tiam1 as a critical factor in the pathophysiology of chronic pain–induced depressive-like behaviors and the sustained antidepressant-like effects of ketamine.
Soluble TREM2 levels associate with conversion from mild cognitive impairment to Alzheimer’s disease
Authors: Aonan Zhao, Yang Jiao, Guanyu Ye, Wenyan Kang, Lan Tan, Yuanyuan Li, Yulei Deng, Jun Liu
Journal: Journal of Clinical Investigation (2022)

BACKGROUND. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) plays an important role in the clearance of pathological amyloid-β (Aβ) in Alzheimer's disease (AD). This study aimed to explore sTREM2 as a central and peripheral predictor of the conversion from mild cognitive impairment (MCI) to AD.
Soluble urokinase plasminogen activator receptor: from biomarker to active participant in atherosclerosis and cardiovascular disease
Authors: Traci T. Goodchild, Zhen Li, David J. Lefer
Journal: Journal of Clinical Investigation (2022)

Atherosclerosis contributes to the majority of deaths related to cardiovascular disease (CVD). Recently, the nonspecific inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) has shown prognostic value in patients with CVD; however, it remains unclear whether suPAR participates in the disease process. In this issue of the JCI, Hindy and colleagues report on their evaluation of a multi-ethnic cohort of over 5,000 participants without known CVD. High suPAR levels correlated with incident CVD and atherosclerosis. Genetic analysis revealed two variants associated with the suPAR-encoding gene (PLAUR) with higher plasma suPAR levels. Notably, a mouse model with high suPAR levels possessed aortic tissue with a proinflammatory phenotype, including monocytes with enhanced chemotaxis similar to that seen in atherogenesis. These findings suggest a causal relationship between suPAR and coronary artery calcification and have clinical implications that extend to inflammatory disorders beyond CVD.
Opioid-induced hyperalgesia: Are thalamic T-type calcium channels treatment targets?
Authors: Slobodan M. Todorovic
Journal: Journal of Clinical Investigation (2022)

Opioid-induced hyperalgesia (OIH) is a state of paradoxically enhanced pain transmission, termed nociceptive sensitization, described to occur in both humans and animals after repeated administration of opioid drugs, including rapidly acting remifentanil. However, molecular mechanisms of OIH remain understudied. In this issue of the JCI, Yan Jin and colleagues provided strong evidence that hyperexcitable thalamocortical networks drive remifentanil-induced hyperalgesia in a rodent model of postsurgical pain. Furthermore, the authors specifically identified an important role of the CaV3.1 isoform of low-voltage-activated or T-type calcium channels (T-channels) in this process. Further experiments are needed to determine whether thalamic T channels could serve as targets for the treatment of OIH.
Regulation of epithelial-mesenchymal transition by tumor microenvironmental signals and its implication in cancer therapeutics
Authors: Jing Zhang, Zhimin Hu, Calista A. Horta, Jing Yang
Journal: Seminars in Cancer Biology (2022)

Epithelial–mesenchymal transition (EMT) has been implicated in various aspects of tumor development, including tumor invasion and metastasis, cancer stemness, and therapy resistance. Diverse stroma cell types along with biochemical and biophysical factors in the tumor microenvironment impinge on the EMT program to impact tumor progression. Here we provide an in-depth review of various tumor microenvironmental signals that regulate EMT in cancer. We discuss the molecular mechanisms underlying the role of EMT in therapy resistance and highlight new therapeutic approaches targeting the tumor microenvironment to impact EMT and tumor progression.
Randomized Trial of Vaccines for Zaire Ebola Virus Disease
Authors: Mark Kieh, Laura Richert, Abdoul H Beavogui, Birgit Grund, Bailah Leigh, Eric D'Ortenzio, Seydou Doumbia, Edouard Lhomme, Samba Sow, Renaud Vatrinet, Céline Roy, Stephen B Kennedy, Sylvain Faye, Shelley Lees, Niouma P Millimouno, Alseny M Camara, Mohamed Samai, Gibrilla F Deen, Moussa Doumbia, Hélène Espérou, Jerome Pierson, Deborah Watson-Jones, Alpha Diallo, Deborah Wentworth, Chelsea McLean, Jakub Simon, Aurélie Wiedemann, Bonnie Dighero-Kemp, Lisa Hensley, H Clifford Lane, Yves Levy, Peter Piot, Brian Greenwood, Geneviève Chêne, James Neaton, Yazdan Yazdanpanah
Journal: New England Journal of Medicine (2022)

Questions remain concerning the rapidity of immune responses and the durability and safety of vaccines used to prevent Zaire Ebola virus disease.
Nanocurcumin combined with insulin alleviates diabetic kidney disease through P38/P53 signaling axis
Authors: Raghu Ganugula, Nikhil K. Nuthalapati, Subhash Dwivedi, Dianxiong Zou, Meenakshi Arora, Richard Friend, David Sheikh-Hamad, Rita Basu, M.N.V. Ravi Kumar
Journal: Journal of Controlled Release (2022)
What Kind of Patients Receive Inpatient and Day-Hospital Treatment in Departments of Psychosomatic Medicine and Psychotherapy in Germany?
Authors: Stephan Doering, Stephan Herpertz, Tobias Hofmann, Matthias Rose, Katrin Imbierowicz, Franziska Geiser, Ilona Croy, Kerstin Weidner, Jörg Rademacher, Silke Michalek, Eva Morawa, Yesim Erim, Per Teigelack, Martin Teufel, Armin Hartmann, Claas Lahmann, Eva Milena Johanne Peters, Johannes Kruse, Dirk von Boetticher, Christoph Herrmann-Lingen, Mariel Nöhre, Martina de Zwaan, Ulrike Dinger, Hans-Christoph Friederich, Alexander Niecke, Christian Albus, Rüdiger Zwerenz, Manfred Beutel, Casper Roenneberg, Peter Henningsen, Barbara Stein, Christiane Waller, Karsten Hake, Carsten Spitzer, Andreas Stengel, Stephan Zipfel, Katja Weimer, Harald Gündel, Henrik Kessler
Journal: Psychotherapy and Psychosomatics (2022)

Introduction: Germany is one of the few countries with a medical specialty of psychosomatic medicine and psychotherapy and many treatment resources of this kind. Objective: This observational study describes the psychosomatic treatment programs as well as a large sample of day-hospital and inpatients in great detail using structured diagnostic interviews. Methods: Mental disorders were diagnosed according to ICD-10 and DSM-IV by means of Mini-DIPS and SCID-II. In addition to the case records, a modified version of the CSSRI was employed to collect demographic data and service use. The PHQ-D was used to assess depression, anxiety, and somatization. Results: 2,094 patients from 19 departments participated in the study after giving informed consent. The sample consisted of a high proportion of “complex patients” with high comorbidity of mental and somatic diseases, severe psychopathology, and considerable social and occupational dysfunction including more than 50 days of sick leave per year in half of the sample. The most frequent diagnoses were depression, somatoform and anxiety disorders, eating disorders, personality disorders, and somato-psychic conditions. Conclusions: Inpatient and day-hospital treatment in German university departments of psychosomatic medicine and psychotherapy is an intensive multimodal treatment for complex patients with high comorbidity and social as well as occupational dysfunction.
Ivermectin Treatment for Covid-19
Authors: Romain Barus, Sophie Gautier, Guillaume Wabont
Journal: New England Journal of Medicine (2022)

Ivermectin Treatment for Covid-19To the Editor: Reis et al. (May 5 issue) 1 present the results of the TOGETHER platform trial, a large trial of ivermectin in outpatients with Covid-19.The relative risk of hospitalization or prolonged observation in the emergency department owing to Covid-19 (the primary outcome) in the ivermectin group as compared with the placebo group was 0.90 (95% Bayesian credible interval, 0.70 to 1.16), and the relative risk of death (a secondary outcome) was 0.88 (95% Bayesian credible interval, 0.49 to 1.55). 1 The prespecified threshold for the clinical utility of ivermectin was a 37.5% difference, as compared with placebo, in the relative risk of a primary-outcome event, a threshold that is probably too conservative for a drug such as ivermectin.The relative risk estimates in the trial were compatible with reductions of up to 30% in the risk of hospitalization or prolonged observation and 51% in the risk of death with ivermectin.Given the wide availability and low cost of ivermectin and that the dosage used in the trial appeared to be safe, such treatment effects could be an important benefit for high-risk patients who do not have access to approved Covid-19 vaccines and costly therapies.The results of the TOGETHER trial were eagerly awaited because of their potential to inform the debate over ivermectin as treatment, 2 but they were arguably nondefinitive 3 regarding the two most relevant outcomes for outpatients with